The role of biosimilars in the treatment of rheumatic diseases

Abstract

The first biological therapeutics in rheumatology are approaching patent expiration, encouraging development of 'follow-on' versions, known as 'biosimilars'. Biological agents range from simple replacement hormones to complex monoclonal antibodies and soluble receptors: large, intricate proteins with unique tertiary and quaternary structures that are inherently difficult to replicate. Post-translational modifications, such as glycosylation, may occur from changes in cell lines and/or manufacturing processes, resulting in products that are highly similar, but not identical, to approved 'reference' agents, hence, the term 'biosimilar', rather than 'bioidentical'. Even minor modifications in manufacturing processes, which iteratively occur with reference products due to improvements in efficiency, scale up to meet commercial demands or changes in manufacturing sites, may alter biological function and/or immunogenicity, potentially changing their safety and efficacy profile. As biosimilars are now in randomised controlled trials for treatment of rheumatic diseases, rheumatologists face decisions regarding equipoise and will need to consider their clinical use versus reference products. A clear understanding of the inherent differences between reference antibodies and biosimilars, their clinical implications and the processes governing regulation, approval and clinical use of biosimilars, is paramount. A panel of international experts in the field of rheumatology recently convened to evaluate and discuss these issues.

Dose reduction of recombinant human tumor necrosis factor inhibitors (etanercept) can be effective in ankylosing spondylitis patients with synovitis of the hip in a Chinese population

“…[9][10][11] Yisaipu®, a recombinant TNFr:Fc with the same structure with etanercept, is a biosimilar subsequent version of etanercept manufactured and marketed in China, which is also commercialized as Etanar in Colombia, as Etart in Mexico, or as Etacept in India. 12 Clinical trials have evidenced Yisaipu® to be effective in a Chinese population. 13 However, recommendations on which patients with AS should be given anti-TNF treatment are especially needed concerning possible side effects and high costs of these drugs.…”

Too Little Too Late: Effect of Poor Access to Biologics for Patients with Rheumatoid Arthritis

“…The advent of biosimilars opens a brave new world of opportunity to reduce the cost of access to biological DMARD 14 . It is our hope that the data from the article by Stamp, et al will open the eyes not just in New Zealand of those who determine access rules for biologics, but also in countries around the world.…”

The rise of biosimilars: potential benefits and drawbacks in rheumatoid arthritis

“…However, the high price of drugs and restricted health care budgets are barriers to easy access to biologic DMARDs. Presumably, the annual cost for prescribing biologic DMARD for a patient ranges from US$10,000 to 25,000, depending on the price policy and health care environment [2]. Therefore, most countries have country-specific guidelines to regulate the reimbursement of biologic agents for RA treatment.…”

“…However, the patents for tocilizumab, adalimumab, rituximab and infliximab will expire in 2015, 2016, 2016 and 2018, respectively, in the USA [2,4,5]. Advances in biotechnology have also enabled developing copy versions of patent-expired originator biologics.…”

“…The biosimilar to infliximab, CTP-13, was studied in RA and ankylosing spondylitis patients, and clinical studies have demonstrated that CTP-13 has equivalent pharmacokinetics and efficacy as well as comparable safety profiles to those of the innovator infliximab [9][10][11]. A true biosimilar agent, approved by the EMA or the US FDA, could be regarded as trustworthy and must be differentiated from the so-called me-too biologics or intended copies, which are on the market in some countries without stringent comparability exercises [2,4].…”